1. ¹Center for Human Genome Research and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China
2. ²Development of Proof-Testing, Renmin Hospital of Tanghe, Tanghe, Henan, People's of Republic of China
3. ³Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic/NE40, Cleveland, OH 44195, USA
4. ⁴Department of Ophthalmology, Union Hospital, Huazhong University of Science and Technology, Wuhan, People's Republic of China
5. ⁵Eye Center, Peking University, Beijing, People's Republic of China

Correspondence: Mugen Liu, Center for Human Genome Research and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China. E-mail: lium@mail.hust.edu.cn; Qing K Wang, E-mail: qkwang@mail.hust.edu.cn

J.Y. Liu and X. Ren contributed equally to this work.

Received 27 January 2007; Accepted 2 April 2007; Published online 22 May 2007.

Abstract

Congenital nystagmus is characterized by involuntary, rhythmical, repeated oscillations of one or both eyes. We studied a large Chinese family with nystagmus as a prominent and consistent manifestation phenotype in nine patients to map and identify a disease-causing gene for nystagmus. X-linked recessive inheritance was observed in the family, and foveal hypoplasia was detected in some of the nine patients. The disease gene was mapped to an approximately 10.6 Mb region flanked by DXS996 and DXS7593 on Xp22 with a significant peak multipoint LOD score. Analysis of 21 candidate genes in the region revealed a novel p.S89F mutation in the second transmembrane domain of GPR143, a G protein-coupled receptor which causes ocular albinism when mutated. All male patients in the family were hemizygous for the mutation; the female carriers were heterozygous for the mutation. The p.S89F mutation was not identified in 100 normal females or 100 normal males. Our results indicate that a mutation in the GPR143 gene can cause a variant form of ocular albinism, with congenital nystagmus as the most prominent and only consistent finding in all patients in this Chinese family. These results expand the spectrum of clinical phenotypes associated with GPR143 mutations.